These studies are aimed at developing a more complete understanding of the origin and functional significance of murine T lymphocytes that have surface membrane Fc receptors. In previous studies, we established that BALB/c mice with subcutaneous plasmacytomas develop large numbers of circulating T lymphocytes that express surface membrane receptors for the heavy chain isotype of the myeloma protein. Since the initiation of this project, we have further established that the myeloma protein induces an expansion of pre-existing T cells with Fc receptors and that this response to the myeloma protein appears to be an exaggerated but otherwise normal immunoregulatory response. The T-alpha cells induced by IgA myeloma protein are Lyt 1-2+ cells which can func-tion as IgA-specific suppressor cells in vivo. Ongoing studies address the mechanisms by which monoclonal immunoglobulins induce the expansion of FcR-bearing lymphocytes, as well as the biochemical events that underly the IgA-specific suppression. T-alpha cell enriched normal lymphocytes as well as cloned lines of T-alpha cells have been shown to suppress the secretion of myeloma protein in vitro in an isotype-specific fashion. Studies are addressing the biochemical events that occur within the suppressed myeloma cells coincident with the cessation of immunoglobulin secretion. Hybridomas that co-express and secrete two monoclonal proteins are being used to examine the specificity of suppression. The information generated in these studies is likely to: (1)\provide insight into the structural basis of immunoglobulin binding to FcR+ lymphocytes; (2)\better define the immunoregulatory functions of FcR+ T cells; and (3)\contribute further to our understanding of the immunology of myeloma.